Abstract
A method was established using a scaffold-bioreactor system to examine the impact pulsatile blood flow has on the decellularized porcine kidney vascular architecture and functionality. These scaffolds were subjected to continuous arterial perfusion of whole blood at normal physiological (650 ml/min and 500 ml/min) and pathophysiological (200 ml/min) rates to examine dynamic changes in venous outflow and micro-/macrovascular structure and patency. Scaffolds subjected to normal arterial perfusion rates observed drops in venous outflow over 24 h. These reductions rose from roughly 40% after 12 h to 60% after 24 h. There were no apparent signs of clotting at the renal artery, renal vein, and ureter. In comparison, venous flow rates decreased by 80% to 100% across the 24 h in acellular scaffolds hypoperfused at a rate of 200 ml/min. These kidneys also appeared intact on the surface after perfusion. However, they presented several arterial, venous, and ureteral clots. Fluoroscopic angiography confirmed substantial alterations to normal arterial branching patterns and patency, as well as parenchymal damage. Scanning electron microscopy revealed that pulsatile blood perfusion significantly disrupted glomerular microarchitecture. This study provides new insight into circumstances that limit scaffold viability and a simplified model to analyze conditions needed to prepare more durable scaffolds for long-term transplantation.